Novel molecular basis of cardriac conduction disturbance associated with a collagene gene mutation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15311
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Nagasaki University
• Principal Investigator: MAKITA Naomasa 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00312356)
• Co-Investigator(Kenkyū-buntansha): 牧山 武 京都大学, 医学研究科, 助教 (30528302)
• Co-Investigator(Renkei-kenkyūsha): ARAI Yuji 独立行政法人国立循環器病研究センター, 研究所, 室長 (30202724) ; ISHIKAWA Taisuke 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60708692)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: コラーゲン / 進行性心臓伝導障害 / ノックインマウス / CRISPR/Cas9

Outline of Final Research Achievements

We found a mutation in type 6 collagen (COL6A2) in several families with progressive cardiac conduction defect. COL6A2 was evenly expressed in mouse ventricular wall during the embryonic stage, which became more restricted at the endocardial wall, age-dependently. At the age of one month, COL6A2 was observed nearly exclusively at the cardiac conduction system. Contrary to our expectation, COL6A2 mutation knock-in mice established by using CRISPR/Cas9 system showed no ECG abnormalities even 12 months after birth.

Free Research Field

循環器内科学